The objectives of this project are to describe the genetic mechanisms and developmental processes in mutant and highly inbred animals with hereditary predisposition to congenital malformations, particularly involving the face and limbs, and to utilize these animals as experimental systems for the study of the processes of congenital malformation. Mouse strains with hereditary malformations as Mendelian or non-Mendelian traits have been discovered in this laboratory or are obtained from others. Comparison of normal and abnormal development are carried out in embryos of timed gestational age using gross examination of living embryos, whole mount preparations and histological sections as well as biochemical analyses of tissues and or cultured organs and cells. Genetic analysis involves segregration analysis, selection of sublines, cross breeding of abnormal and normal lines and genetic linkage studies. Agents such as drugs, vitamins and hormones are used as probes for the study of gene action in hereditary malformations and for the study of possible human teratogens. BIBLIOGRAPHIC REFERENCES: Ross, M.E., Onodera, T., Brown, K.S. and Notkins, A.L.: Virus-induced diabetes mellitus. IV. Genetic and environmental factors influencing the development of diabetes after infection with the M variant of encephalonyocarditisvirus. Diabetes 25: 190-197, 1976. Orkin, R.W., Williams, B., Cranley, R., Poppke, D. and Brown, K.: Defects in the cartillagenous growth plates of Brachymorphic mice. J. Cell Biol. 73: 287-299, 1977.